Metabolic imaging of tumors using intrinsic and extrinsic fluorescent markers.
Metabolic imaging of tumors using intrinsic and extrinsic fluorescent markers.
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DOI：
10.1016/j.bios.2004.03.034
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发表时间：
2004-10
影响因子：
12.6
通讯作者：
Zhihong Zhang;Hui Li;Qian Liu;Lanlan Zhou;Min Z. Zhang;Qingming Luo;J. Glickson;B. Chance;G. Zheng
中科院分区：
文献类型：
--
作者：
Zhihong Zhang;Hui Li;Qian Liu;Lanlan Zhou;Min Z. Zhang;Qingming Luo;J. Glickson;B. Chance;G. Zheng
恶性肿瘤的生化“标志”之一是肿瘤糖酵解增强，这主要是由于肿瘤中葡萄糖转运蛋白（GLUT）的过度表达和线粒体结合己糖激酶的活性增加所致。评估体外和体内葡萄糖利用的简单方法应该在生物学和生物医学研究中得到广泛应用，正如 FDG PET 成像在医学中的应用所证明的那样。我们最近合成了一种新的 2-脱氧葡萄糖 (2DG) 近红外荧光焦脱镁叶绿酸缀合物 Pyro-2DG，作为 GLUT 靶向光敏剂。在本研究中，我们评估了 Pyro-2DG 的体内摄取，发现 Pyro-2DG 在两种肿瘤模型（大鼠 9L 神经胶质瘤和小鼠 c-MYC 诱导的乳腺肿瘤）中选择性积累，与周围正常肌肉组织相比，比例约为 10:1。通过同时进行氧化还原比和荧光成像，PN/(Fp+PN)氧化还原比之间存在高度相关性，其中PN表示还原吡啶核苷酸(NADH)，Fp表示氧化黄素蛋白，并且在两种小鼠肿瘤模型中都发现Pyro-2DG摄取，表明Pyro-2DG可以作为肿瘤的外在NIR荧光代谢指标。事实上，氧化还原比和 Pyro-acid（不含 2-脱氧葡萄糖部分的游离荧光团）的摄取之间仅观察到低水平的相关性，这一事实支持了 Pyro-2DG 是肿瘤线粒体状态（PN 减少程度）指标的假设。
One of the biochemical “hallmarks” of malignancy is enhanced tumor glycolysis, which is primary due to the overexpression of glucose transporters (GLUTs) and the increased activity of mitochondria-bound hexokinase in tumors. Easy methods for assessing glucose utilization in vitro and in vivo should find widespread application in biological and biomedical studies, as illustrated by the adoption of FDG PET imaging in medicine. We have recently synthesized a new NIR fluorescent pyropheophorbide conjugate of 2-deoxyglucose (2DG), Pyro-2DG, as a GLUT-targeted photosensitizer. In this study, we have evaluated the in vivo uptake of Pyro-2DG and found that Pyro-2DG selectively accumulated in two tumor models, 9L glioma in the rat and c-MYC-induced mammary tumor in the mouse, compared to surrounding normal muscle tissues at a ratio of about 10:1. By simultaneously performing redox ratio and fluorescence imaging, a high degree of correlation between the PN/(Fp+PN) redox ratio, where PN denotes reduced pyridine nucleotides (NADH) and Fp denotes oxidized flavoproteins, and the Pyro-2DG uptake was found in both murine tumor models, indicating that Pyro-2DG could serve as an extrinsic NIR fluorescent metabolic index for the tumors. The fact that only a low level of correlation was observed between the redox ratio and the uptake of Pyro-acid (the free fluorophore without the 2-deoxyglucose moiety) supports the hypothesis that Pyro-2DG is an index of the mitochondrial status (extent of PN reduction) of a tumor.